The First Deuterated Drug Arrives | Hacker News Reader

The First Deuterated Drug Arrives

blogs.sciencemag.org

66 pointsadenadel32 comments

I expect we will see a slew of out-of-patent drugs re-created with deuterium atoms for marginal clinical benefit and then sold under patent again.

That might happen, but nothing would stop people from using the much cheaper generic of the original drug.

Nothing except their doctor recommending the more expensive name brand drug, which happens all the time. I'm sure there are many reasons why this happens including drug companies having cosy relationships with doctors and also consumer advertising causing patients to request specific drugs.

Take Nexium.[1] I'm no expert, but I understand Nexium to be esomeprazole, the s-isomer of omeprazole which is to say it's a mirror image chemically. Yet it's the second most prescribed drug in America.

1. http://scienceblogs.com/denialism/2012/01/09/why-no-one-shou...

and hospitals.

If it's a prescription drug, then the doctor might write a prescription for the name brand drug. It's possible for a prescription not to allow a generic substitute, and it seems particularly easy to do in a case like this where the name-brand drug is not identical to the generic.

It's not the mirror image of omeprozle (Prilosec, which is both isomers), it's just manufactured so that only one isomer is present in the pills.

The same gag with https://en.wikipedia.org/wiki/Levocetirizine and cetirizine. Levocetirizine just became available OTC in the US and costs 3x more than generic cetirizine (for dubious benefit).

I know that this isn't an option everywhere, but I get my healthcare through an HMO and they will have quite the opposite philosophy. Instead of trying to sell the patient on more expensive drugs, they will actually refuse to prescribe or cover drugs that have a cheaper alternative.

Most US insurance plans have a formulary and will not cover all drugs.

I've fortunately not had much need for prescription drugs but have almost always been prescribed cheap generics. I think this is a fairly common experience.

There can be a real benefit to isomer drugs. They get prescribed way more than they need to, no question, but that doesn't make them entirely useless.

For example, desvenlafaxine (Pristiq) is the R-isomer of venlafaxine (Effexor). You'd think it would be a useless me-too drug, but in fact it's metabolized differently, which affects people with CYP450 mutations. Ultrarapid metabolizers will end up with way too little Effexor in their system, whereas Pristiq will work fine for them. Other way around with poor metabolizers: they don't metabolize Effexor well enough, so they'll get worse side effects. (See http://psychopharmacologyinstitute.com/antidepressants/snris... and specifically http://psychopharmacologyinstitute.com/wp-content/uploads/12...)

Ideally we'd all know our CYP450 profile, or our doctors would, so they could prescribe older and cheaper drugs when they work well enough, and save the new expensive stuff for patients who need it. Maybe someday medicine will come around to using the tools it already has at hand. Sigh.

That it is sometimes important makes the (apparent) sham use of the distinction all the much worse.

> I'm sure there are many reasons why this happens

A simpler reason is that the drop-down on computerised notes systems sometimes puts the more expensive version first.

https://twitter.com/drmarkporter/status/765569736423927813

> Q for SystmOne GPs: is there a simple way to ensure default drugs offered when prescribing are cheapest versions most commonly prescribed?

https://twitter.com/drmarkporter/status/765570038048911360

> For context: our default omeprazole version (20mg) is currently 5 times price of one 4 down. Easily repeated costly error when busy.

In order to get a generic approved you need to do testing that shows your drug works in the same way as the original. In order to have a control you need to have the original drug, thus a pharma company can stop production on a drug while still under patent and replace it with this "new" drug (often the same drug with an antacid added) thus making generic approval much more difficult and costly.

Not in this case; the main effect of deuteration is to slow the rate at which the active drug is metabolized and excreted.

Now, that might not sound significant — but patient compliance with medication regimes is a significant sticking point in clinical practice; people are generally just terrible about taking their meds on schedule. If you can replace a twice-a-day tablet with a once-a-day treatment, that's a big win for the subset of patients who are forgetful/unreliable at taking their meds twice a day — and in a disease where the symptoms progress to dementia, that's important.

More on medication compliance here (some of it quite hair-raising):

https://en.wikipedia.org/wiki/Adherence_(medicine)

> Not in this case; the main effect of deuteration is to slow the rate at which the active drug is metabolized and excreted.

this reminds me of deuterating DMT (dimethyltryptamine) in order to fortify bonds that are targeted by MAO -- to avoid the need for pretreatment with a MAO inhibitor (a MAOI -- which tend to be nasty because of all their interactions)

I take two Janumet (metformin and sitagliptin) per day, made by Merk and still in-patent. They make an XR (extended release) version, where you only take one per day. I can see a deuterium version extending the patent rails for another N years.

An interesting topic to look into is the effect of deuterium on longevity in various species. It appears to induce a form of hormesis at low levels (perhaps) or improve resistance of certain important cell structures to oxidative damage (perhaps). [1]

The company Retrotope [2] is trying to do something with what is known of this biochemistry.

Deuterated drugs after the fashion of the one in this article are probably not going to be delivering enough deuterium to trigger this sort of effect, however.

[1]: http://onlinelibrary.wiley.com/doi/10.1002/bies.201600040/fu...

[2]: https://www.retrotope.com/

What's interesting is that Concert Pharmaceuticals (Derek mentions this in his post) has been working on this technology for the past two decades. I'm kind of surprised they weren't the first to market.

Drug R&D is hard!

Everything is hard with software being a notable exception.

Boy have I got a bridg... err.. 'framework' to sell to you.

I don't know who you think you are. Coming on here and saying things like this. How dare you.

as the article probably said..this is adding deuterium to an old drug that has been around for a while. The pharma for the old stuff is Lundborg, supposedly one of the "non-profit" pharmas focused on orphan drugs. Pricing is high, mostly due to supply constraints, so they say, but the foundation attached to the company gives patients some sort of financial advice.

Basically, the drug induces a form of parkinsonism (hypokineticism) to combat conditions that cause hyperkineticism.

I'm interested in seeing how the patent issues turn out around reiterated drugs in the future.

I predict that they will be and remain patentable. I'm no lawyer, but deuteration does not seem obvious. Yes the idea that you can swap out hydrogen for deuterium is obvious, but the idea that deuteration will have a meaningful effect on a specific drug is not. For some drugs it may do nothing while in others it will.

When the drug finally gets metabolized, are there any effects of a higher presence of deuterium in the body to be expected?

$60,000 usd a year list price.

To play the devil's advocate, there are 30,000 people in the US with Huntington's [0]. If all of them paid full price for the drug that comes out to 1.8B. Bringing a drug to market costs 2.5B [1]. In order to encourage drug development for rare diseases, there needs to be some financial reward. Often more than half of a drug's patent is gone by the time that the drug is approved.

0. http://www.medicalnewstoday.com/articles/159552.php

1. https://www.scientificamerican.com/article/cost-to-develop-n...

Drug developers have a strong incentive to overstate what they spent developing a drug. Since they are the source of these numbers, I suspect they are inflated. If you were to take all of the drugs a company developed during some time period and add up their reported development costs the total would likely far exceed the companies total expenditure.

That's a strong claim that you could probably support with data with little effort, but as it stands, it's conjecture.

I do agree with your analysis, but it's a weak argument to incentive.

Their potential market is worldwide, and getting your R&D money back in a year or so is extremely good.

I'm pretty sure the $2.5 billion/drug includes R&D "wasted" on failed drugs too. The industry gets 20-30 new drugs approved per year, and spends around $60 billion per year developing them. I mention this because one could easily see that figure and think that they'd need to make, say, $25 billion just to break even after paying for all the drugs that never made it out of development.

VMAT2 target has me considering some.. interesting.. hypothetical deuteronomical creations.

I like the pun, but Hamer's work isn't well supported. I won't even ask what you had in mind.

Hah, I hadn't even noticed that pun. I was thinking of the drug target. And maybe if Walter White would, in another universe, be cooking "heavy meth"

Heavy versions of most performance enhancers have been "available" for decades, for obvious reasons.

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